How scientists used drugs to turn skin cells into heart, brain cells

NEW DELHI: In a major step in regenerative medicine, scientists in the US turned skin cells into heart and brain cells by using a cocktail of chemicals. The two studies, which were published in Science and Cell Stem Cell journals, are especially remarkable as the scientists did not add any external genes to the cells, a usual requirement.

The research could be the base for one day being able to regenerate lost or damaged cells with pharmaceutical drugs. The team of scientists used chemical cocktails to force skin cells to convert into organ-specific stem cell-like cells and, finally, into heart or brain cells.

“This method brings us closer to being able to generate new cells at the site of injury in patients,” said Gladstone senior investigator Sheng Ding, PhD, and senior author on both studies. “Our hope is to one day treat diseases like heart failure or Parkinson’s disease with drugs that help the heart and brain regenerate damaged areas from their own existing tissue cells.”

The researcher further added that this process is much closer to the natural regeneration that happens in animals such as newts and salamanders.

Adult hearts are not highly capable of producing new cells and so scientists have been looking for ways to replace the cells of a damaged heart, say after a heart attack.

However, as most transplanted adult cells do not survive or do not adapt properly into the heart, and very few stem cells can be converted into heart cells, the endeavor has been tricky.

In the study published in Science journal, the researchers used a cocktail of nine chemicals to change human skin cells into beating heart cells. By trial and error, they found the best combination of chemicals, which could change the cells into a state close to multi-potent stem cells, which are capable of turning into many different types of cells in a particular organ. A second cocktail of chemicals and growth factors facilitated the transition the cells to become heart muscle cells.

With this method, more than 97 percent of the cells began beating, a characteristic of fully developed, healthy heart cells. The cells also responded appropriately to hormones, and molecularly, they resembled heart muscle cells, not skin cells. When the cells were transplanted into a mouse heart early in the process, they developed into healthy-looking heart muscle cells within the organ.

“The ultimate goal in treating heart failure is a robust, reliable way for the heart to create new muscle cells,” said Deepak Srivastava, MD, director of cardiovascular and stem cell research at Gladstone and co-senior author on the Science paper. “Reprogramming a patient’s own cells could provide the safest and most efficient way to regenerate dying or diseased heart muscle.”

In the second study, published in Cell Stem Cell, the scientists created neural stem cells from mouse skin cells using a similar approach.

A combination of chemicals converted all the skin cell genes into neural stem cell genes. When transferred into mice, the neural stem cells developed into the three basic types of brain cells: neurons, oligodendrocytes, and astrocytes.

“With their improved safety, these neural stem cells could one day be used for cell replacement therapy in neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease,” said co-senior author Yadong Huang, MD, PhD, a senior investigator at Gladstone.

Huang added, “In the future, we could even imagine treating patients with a drug cocktail that acts on the brain or spinal cord, rejuvenating cells in the brain in real time.” TNS